Endocrine Abstracts

The key factor in the pathogenesis of both T2D and NAFLD is insulin resistance, which causes the lipids accumulation in hepatocytes and an increase of the lipid peroxidation, the production of reactive oxygen species and the development of inflammation. It has been shown that the main metabolic products of the saccharolytic microflora-short-chain fatty acids (SCFA), such as acetic (Ac), propionic (Pr) and butyric (Bu), can have an anti-inflammatory effect through their suppression of histone deacetylase (HDAC) activity (Arpaia N et al., 2013).

The aim

To study the features of bacterial metabolism in the colon in patients with T2D and NAFLD in comparison with the activity of the lipid peroxidation process.

Materials and methods

The study included 46 patients with T2D and NAFLD, mean age – 56.4 ± 7.2 y. The activity of lipid peroxidation process was assessed by conc. of malondialdehyde (MDA) in blood. The concentrations of fecal SCFA (Ac, Pr, Bu, valerian acid and their isoforms) were determined by GLC- method.

Results

It was shown that the average blood MDA level in T2D + NAFLD patients was increased by 70% and amounted to 17.4 ± 1.3 mmol/l vs norm (N) - 10.1 ± 0.8 mmol/l (P < 0.001). The value of total SCFA (TSCFA) was reduced and averaged 8.6 ± 2.8 mg/g vs N 10.6 ± 2.6 mg/g, P < 0.01. In the structure of the metabolites, there was a decrease in the proportion of butyrate (T2D + NAFLD 12.1 ± 0.8% vs N 16.0 ± 0.6%, P < 0.001) and an increase of propionate one (T2D + NAFLD 23.1 ± 0.5% vs N 20.0 ± 0.6%, P < 0.001). In T2D + NAFLD patients in stage оf steatohepatitis, there was a more pronounced decrease in total metabolic activity due to a decrease in conc. of butyrate. In addition, there was an increase in the proportion of iso-acids, metabolites of the proteolytic microflora (9.4 ± 0.7% vs N 6.3 ± 0.04%, P < 0.02). In order to assess the degree of anti-inflammatory action of microbiota, a correlation analysis was performed between conc. MDA and SCFA. There were significant correlations between the TSCFA (r = –0.437; P = 0.049), acetate (r = –0.4550; P = 0.024), propionate (r = –0.375; P = 0.037) and conc. MDA.

Conclusion

Thus, a decrease in the total metabolic activity of the colon microflora in T2D + NAFLD occurs due to a decrease in the activity of Bu-producing and an increase in Pr – producing bacteria. Inverse correlation conc. SCFA and MDA indicate a pronounced effect of the luminal SCFA on the processes of inflammation in T2D with NAFLD patients.